Fate Therapeutics Announces FDA Clearance for FT536, a First-in-class MICA/B-targeted CAR NK Cell Product Candidate for the Treatment of Solid Tumors

Multiplexed-engineered CAR NK Cell Product Candidate derived from Clonal Master iPSC Line that incorporates Four Functional Elements, including a Novel CAR Targeting the Pan-tumor Associated Stress Proteins MICA and MICB

Proprietary Antigen Binding Domain of FT536 has been Shown to Overcome MICA/B Shedding, a Common Mechanism of Tumor Cell Escape Broadly Observed Across Solid Tumors

Six-arm Phase 1 Clinical Study to Evaluate Multi-dose, Multi-cycle Treatment Schedule of FT536 as Monotherapy and in Combination with Monoclonal Antibody Therapy for Patients with Advanced Solid Tumors

SAN DIEGO, Calif., Jan. 10, 2022 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for FT536, an off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor (CAR) NK cell product candidate. FT536 is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional elements, including a novel CAR that uniquely targets the α3 domain of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB). MICA and MICB are stress proteins that are expressed at high levels on many solid tumors. The Company plans to initiate clinical investigation of FT536 as a monotherapy and in combination with tumor-targeting monoclonal antibody therapy for the treatment of multiple solid tumor indications.

“We are very pleased with our progress in bringing first-in-class, multiplexed-engineered NK cell product candidates to patients for the treatment of solid tumors. MICA and MICB are emerging as exciting pan-cancer immunotherapy targets across a wide range of solid tumors, and FT536 represents a novel therapeutic strategy designed to target these stress-induced ligands,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “With the proteolytic shedding of the α1 and α2 domains of MICA/B being recognized as a common tumor escape mechanism, we are encouraged that our novel CAR design, which uniquely targets the α3 domain of MICA/B, has shown the potential to overcome shedding and restore NK and T cell-mediated tumor immunity. We look forward to treating patients with FT536 as monotherapy and in combination with monoclonal antibody therapy to promote a multi-pronged attack against solid tumors.”

FT536 also incorporates a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments such as the suppressive tumor microenvironment. The multi-center Phase 1 clinical trial of FT536 is designed to determine the maximum tolerated dose of FT536 and assess its safety and clinical activity as monotherapy and in combination with one of an array of five monoclonal antibodies for the treatment of advanced solid tumors. Eligible tumor types include advanced non-small cell lung cancer, colorectal cancer, head and neck cancer, gastric cancer, breast cancer, ovarian cancer, and pancreatic cancer.

The Phase 1 clinical protocol allows for administration of FT536 initially in up to two, 30-day cycles, with each cycle consisting of three days of conditioning chemotherapy and three weekly doses of FT536. Patients with clinical benefit may be re-treated with up to two additional cycles. Furthermore, for those patients that achieve initial clinical response, additional treatment with FT536 may be administered following disease progression. The off-the-shelf treatment regimen is designed to be administered in the outpatient setting.

The expression of MICA and MICB proteins, which is induced by cellular stress, damage or transformation, has been reported for many solid tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can recognize and bind the membrane-distal α1 and α2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B. A recent publication in Science (DOI:10.1126/science.aao0505) by Kai W. Wucherpfennig, M.D., Ph.D., Chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and co-leader of the Cancer Immunology Program at Dana-Farber / Harvard Cancer Center, demonstrated that antibody targeting of the MICA/B α3 domains specifically prevents MICA/B shedding and restores NK cell-mediated immunity. Additionally, in a more recent publication in Cancer Immunology Research (DOI: 10.1158/2326-6066.CIR-19-0483), Dr. Wucherpfennig also demonstrated that cancers with B2M and JAK1 inactivating mutations resulting in loss of MHC Class I expression can be effectively targeted with MICA/B α3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors resistant to cytotoxic T cells. The Company’s FT536 program is supported by an exclusive license from the Dana-Farber Cancer Institute to intellectual property covering novel antibody fragments binding MICA/B for iPSC-derived cellular therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Company’s immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.

Forward-Looking Statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company's product candidates and clinical studies, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, the therapeutic potential of the Company’s product candidates including FT536, and the Company’s clinical development strategy for FT536. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk of difficulties or delay in the initiation of any planned clinical studies, or in the enrollment or evaluation of subjects in any ongoing or future clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT536 may not be replicated in ongoing or future clinical trials or studies, and the risk that FT536 may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:
Christina Tartaglia
Stern Investor Relations, Inc.
212.362.1200
christina@sternir.com